Longitudinal evaluation of cognitive performance in multiple sclerosis and the influence of fatigue, sleepiness, and depressive symptoms

Abstract

Background: Cognitive impairment is a frequent manifestation in multiple sclerosis and may occur at different stages of the disease, significantly affecting daily functioning and quality of life. Longitudinal cognitive assessment allows a better understanding of how these changes evolve over time. However, cognitive performance may be influenced by clinical and methodological factors, including neuropsychiatric symptoms and possible learning effects related to repeated testing. Objective: To evaluate cognitive changes over time in patients with multiple sclerosis and to investigate the influence of fatigue, sleepiness, and depressive symptoms on cognitive performance. Methods: Patients with multiple sclerosis were longitudinally assessed using a standardized brief cognitive battery applied during multiple follow-up visits. Cognitive scores were converted into standardized values adjusted for age and education. Two versions of the cognitive battery were used during follow-up, allowing control for possible learning effects related to repeated testing. Statistical analysis was performed using linear mixed models for longitudinal data, considering the standardized global cognitive score as the dependent variable. Independent variables included time since baseline assessment, visit, version of the cognitive test applied, sex, ancestry, clinical phenotype of the disease, and the scores of fatigue, sleepiness, and depression assessed at each visit. A random intercept for each participant was included to account for correlations between repeated measurements. Results: A significant effect of visit on cognitive performance over time was observed (F = 3.443; p = 0.019), indicating variation in cognitive scores across follow-up assessments. Higher fatigue levels showed a tendency to be associated with lower cognitive performance (β = −0.008; p = 0.069). Sleepiness (p = 0.417) and depressive symptoms (p = 0.525) were not significantly associated with cognitive performance. Demographic variables, including sex and ancestry, were also not significantly associated with cognitive scores. Substantial variability between individuals was observed, with an intraclass correlation coefficient of 0.785. Conclusion: Cognitive performance in patients with multiple sclerosis varies over longitudinal follow-up. Fatigue showed a possible influence on cognitive performance, while sleepiness and depressive symptoms were not significantly associated with cognitive outcomes in this model. These findings highlight the importance of structured longitudinal cognitive assessment and the consideration of clinical factors that may influence cognitive performance in patients with multiple sclerosis.